Publications

Funding for clinical research |drugs, vaccines, microbicides, diagnostics | HIV/AIDS, tuberculosis, malaria, other infectious diseases |sub-Saharan Africa

The PredictTB study is investigating whether a combination of biomarkers can identify TB patients who are responding well to antibiotics so their treatment can be halted early.

Identifying TB patients suitable for shortened treatment

Reducing treatment times from six to four months is a major goal in TB research. Shorter treatment times would reduce costs, increase compliance and reduce the risk of drug resistance.

In clinical trials, four-month regimens have generally not been as successful as standard six-month treatments. However, 80–85% of participants are cured at four months. If these patients could be identified reliably, their treatment could safely be stopped early. 

The challenge

The PredictTB team has identified a combination of markers, based on radiographic examination of lungs and detection of Mycobacterium tuberculosis by Xpert molecular diagnostic technology, that are good predictors of individuals who respond well to therapy and whose treatment could be stopped at four months.

To evaluate these markers, the team is running a phase IIb clinical trial on more than 600 patients with drug-sensitive pulmonary TB. All patients are receiving standard TB treatment for 16 weeks; at this point, radiographic and Xpert results are being used to distinguish ‘poor responders’, who will continue with the full six-month course, and ‘good responders’, who will be randomised to continued therapy or early completion. Cure rates will then be compared at 18 months.

The PredictTB project has received support from a range of funders, including the Bill & Melinda Gates Foundation, and is recruiting patients at multiple sites in China as well as South Africa.

The sophisticated radiographic tools used to identify good responders would not be suitable for routine use in low-resource settings. The project is therefore also investigating other possible biomarkers that are associated with good response to treatment, which could be used as alternatives to radiographic screening. This is informing the development of a more practical point-of-care test that could be used to identify patients suitable for early completion of therapy. The project is also developing a biobank of samples for future biomarker research.

The project

The PredictTB study could provide the tools to enable large numbers of TB patients to finish TB therapy early, even with currently used drugs. This would benefit patients, reducing their exposure to powerful drugs and a daily drug-taking routine, as well as health systems, by reducing costs of treatment.

Impact


crucial in

widening African

children’s access

to antiretrovirals

Bringing antiretroviral drugs to children

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

EDCTP portfolio: HIV & HIV-associated infections

The challenge

Reducing treatment times from six to four months is a major goal in TB research. Shorter treatment times would reduce costs, increase compliance and reduce the risk of drug resistance.

In clinical trials, four-month regimens have generally not been as successful as standard six-month treatments. However, 80–85% of participants are cured at four months. If these patients could be identified reliably, their treatment could safely be stopped early. 

The PredictTB team has identified a combination of markers, based on radiographic examination of lungs and detection of Mycobacterium tuberculosis by Xpert molecular diagnostic technology, that are good predictors of individuals who respond well to therapy and whose treatment could be stopped at four months.

To evaluate these markers, the team is running a phase IIb clinical trial on more than 600 patients with drug-sensitive pulmonary TB. All patients are receiving standard TB treatment for 16 weeks; at this point, radiographic and Xpert results are being used to distinguish ‘poor responders’, who will continue with the full six-month course, and ‘good responders’, who will be randomised to continued therapy or early completion. Cure rates will then be compared at 18 months.

The PredictTB project has received support from a range of funders, including the Bill & Melinda Gates Foundation, and is recruiting patients at multiple sites in China as well as South Africa.

The sophisticated radiographic tools used to identify good responders would not be suitable for routine use in low-resource settings. The project is therefore also investigating other possible biomarkers that are associated with good response to treatment, which could be used as alternatives to radiographic screening. This is informing the development of a more practical point-of-care test that could be used to identify patients suitable for early completion of therapy. The project is also developing a biobank of samples for future biomarker research.

The project

The later CHAPAS-3 trial compared the efficacy and safety of three fixed-dose combinations including two without stavudine (found to have some long-term side effects in adults, leading to a recommendation that its use be discontinued in children). The trial the first of its kind in Africa studied nearly 500 children at four sites in two African countries.

The PredictTB study could provide the tools to enable large numbers of TB patients to finish TB therapy early, even with currently used drugs. This would benefit patients, reducing their exposure to powerful drugs and a daily drug-taking routine, as well as health systems, by reducing costs of treatment.

ratios forfixed-dose combinations and on appropriatedosage according to weight. 

The CHAPAS-3 trial confirmed the effectiveness of fixed-dose combinations, providing further impetus to the rollout of antiretrovirals to children. Its evidence on abacavir informed the WHO recommendation of abacavir-containing combinations for first-line therapy in children. Trial data have also been used to support applications for regulatory approval for new scored efavirenz tablets.

Impact

L’homme RF et al. Nevirapine, stavudine and lamivudine pharmacokinetics in African children on paediatric fixed-dose combination tablets. AIDS. 2008;22(5):557–65.

Mulenga V et al. Abacavir, zidovudine, or stavudine as paediatric tablets for African HIVinfected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial. Lancet Infect Dis. 2016;16(2):169–79.

WHO. Guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2010.

WHO. Consolidated guidelines on the use of antiretroviral drugs
for treating and preventing

HIV infection: Recommendations for a public health approach
(second edition). 2016

Projects: Children with HIV in Africa Pharmacokinetics and Adherence of Simple Antiretroviral Regimens (CHAPAS): CHAPAS-1 and -3

Project lead: Professor Chifumbe Chintu, University Teaching Hospital, Zambia (CHAPAS-1); Dr Veronica Mulenga, University Teaching Hospital, Zambia (CHAPAS-3)

Target population(s): Children with HIV

Sample size: 71 (CHAPAS-1); 480 (CHAPAS-3)

Countries involved: Ireland, the Netherlands, the UK, the USA, Zambia (CHAPAS-1); Uganda, Zambia (CHAPAS-3)

Project duration: 2005–2009 (CHAPAS-1); 2010 –2011 (CHAPAS-3)

EDCTP funding: €1.2M (CHAPAS-1); €4.6M (CHAPAS-3)

Total project funding: €1.2M (CHAPAS-1); €5.0M